Analyte detection in physiological fluids, e.g. blood or blood derived products, is of ever increasing importance to today's society. Analyte detection assays find use in a variety of applications, including clinical laboratory testing, home testing, etc., where the results of such testing play a prominent role in diagnosis and management in a variety of disease conditions. Analytes of interest include glucose for diabetes management, cholesterol, and the like. In response to this growing importance of analyte detection, a variety of analyte detection protocols and devices for both clinical and home use have been developed.
One type of method that is employed for analyte detection is an electrochemical method. In such methods, an aqueous liquid sample is placed into a sample-receiving chamber in an electrochemical cell that includes two electrodes, e.g., a counter and working electrode. The analyte is allowed to react with a redox reagent to form an oxidizable (or reducible) substance in an amount corresponding to the analyte concentration. The quantity of the oxidizable (or reducible) substance present is then estimated electrochemically and related to the amount of analyte present in the initial sample.
Such systems are susceptible to various modes of inefficiency and/or error. One of the blood glucose measurement manufactured by LifeScan Inc., and marketed as One-Touch Verio (“Verio”) has remarkably good overall performance with regards to resisting the effects of hematocrit and interfering reducing agents such as uric acid. Nevertheless, interferents such as reducing agents in the form of uric acid may affect the results of the method. Specifically, there is observed to be a potential hematocrit dependence from applicant's blood glucose data. As an example, consider a situation in which an electroactive species such as uric acid or ferrocyanide is uniformly distributed in the Verio test strip cell. Measurements taken immediately after switching potential are in a regime where the developing concentration gradient is semi-infinite: it has not yet moved out far enough into the cell that it is influenced by the gradient developing at the opposite electrode.
Another observation was the effect of endogenous reducing agents such as uric acid, independent of glucose. It is believed that Verio test strip uses the 1.1 second current to account for interferences by predicting the magnitude of interference current in the third pulse measurements based on the 1.1 second current:
                              i          ⁢                                          ⁢          2          ⁢                                          ⁢          corr                =                              (                                                                                                  i                    ⁢                                                                                  ⁢                    4.1                                                                    +                                  b                  ⁢                                                                                i                      ⁢                                                                                          ⁢                      5                                                                                          -                                  2                  ⁢                                                                                i                      ⁢                                                                                          ⁢                      1.1                                                                                                                                                                              i                    ⁢                                                                                  ⁢                    4.1                                                                    +                                  b                  ⁢                                                                                i                      ⁢                                                                                          ⁢                      5                                                                                                                )                    ⁢                      i            R                                              (        7        )                            where b˜0.678        
It would appear that this function is intended to find the fraction of iR that is due solely to glucose by using a function that goes to 1 if here is no interference (i1.1=0) or 0 if there is interfering reducing agent current but no glucose (i4.1, i5 comprising only interference currents). If this is the case, i2corr should be independent of interfering reducing agent.
Experiments show that while i2corr does a good job of removing the uric acid dependence of iR at medium to high glucose, it does so incompletely at low glucose. But in spite of this fairly successful correction of iR, the glucose results Gbasic (glucose results prior to correction(s)) are significantly influenced by uric acid, especially at high glucose.
The formula for glucose result is:
                    Gbasic        =                                            [                                                                                      i                    R                                                                                                                            i                    L                                                                                ]                        p                    ⁢                      (                                          a                ⁢                                                                        i                    ⁢                                                                                  ⁢                    2                    ⁢                                                                                  ⁢                    corr                                                                                -              zgr                        )                                              (        7.5        )                            Where                    p˜0.523            a˜0.14            zgr˜2                        
It is believed that while Gbasic has a strong uric acid dependence at high glucose, i2corr did not, and therefore it is apparent that the hematocrit compensation function is not working correctly when challenged with both high glucose and high interfering reducing agent levels. Part of this problem is undoubtedly due to the fact that iL (sum of current from 1.4 to 4 seconds) is strongly influenced by interfering reducing substances.
It is noted that iL is composed of an essentially steady state current from interfering reducing agents and a growing glucose current due to ongoing diffusion of ferrocyanide and enzyme from the second electrode. Uric acid has a substantially larger effect on iL than it does on iR. The analysis above showed how the hematocrit compensation function should work by compensating for the effect of Red-Blood-Cells', assuming only glucose current was being detected. The hematocrit compensation function is really not designed to work correctly at different levels of interfering reducing agent. It is believed that what happens is that at high glucose, iL increases, causing inappropriately small values of the hematocrit compensation function and low glucose results.
Because |i2corr| increases with increasing uric agent, the effect of decreasing interference correction function is partially compensated. But no such compensation happens at high glucose, where i2corr works better. Thus it appears that there is an overcompensation for interfering reducing agents at high glucose, in reality the inputs to the hematocrit compensation function are being interfered with, causing incorrect hematocrit compensation.